Investigating the Interactions of AZD0530 With Alcohol in Social Drinkers

A Phase 1 Study Investigating the Interactions of AZD0530 With Alcohol in Social Drinkers

The purpose of this alcohol-interaction pilot study is to provide information on the effect of AZD0530 (Saracatinib) on the pharmacokinetics of alcohol and on alcohol responses, including stimulation, sedation, intoxication, body sway and physiological responses. The investigators propose to test the effects of a single dose of AZD0530 (125 mg) on alcohol related responses. This is a within subjects open label study in which the investigators plan to run 8 subjects to obtain 5 completers.

Study Overview

• Status: Completed
• Conditions: Alcohol Drinking
• Intervention / Treatment: Drug: Saracatinib

Detailed Description

The purpose of this alcohol-interaction pilot study is to provide information on the effect of AZD0530 (Saracatinib) on the pharmacokinetics of alcohol and on alcohol responses, including stimulation, sedation, intoxication, body sway and physiological responses. The investigators propose to test the effects of a single dose of AZD0530 (125 mg) on alcohol related responses. This is a within subjects open label study in which the investigators plan to run 8 subjects to obtain 5 completers.

Subjects will participate in two lab sessions, one prior to taking medication and one following 8-11 days of AZD0530. During each session, participants will receive successive doses of alcohol over a 90 min period designed to raise their blood alcohol levels to 80 mg/dl; this dose was chosen because this is close to the legal limit of intoxication and to the peak blood alcohol content (BAC) we have observed in prior research studies.Subjects will be monitored throughout the lab session and will receive a phone call two days following the 2nd lab session and a follow-up appointment one week after the 2nd lab session to assess any remaining side effects from the medication.

Once it is determined that there is no change in the pharmacokinetics of alcohol or AZD0530, as well as no difference in behavioral or cognitive responses to alcohol in the presence of AZD0530, the investigators will begin the pilot study examining the effects of two doses of AZD0530 on behavioral measures related to alcohol self-administration following a fixed dose of alcohol in alcohol abusive or dependent heavy drinkers, and compare responses to those obtained from historical controls who were treated with placebo in Study 1. Subjects will be randomized to one of two doses of AZD0530 (50 mg/day or 125 mg/day) as a between subjects factor.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • CMHC, Substance Abuse Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Ages 21-50
2. Able to read English at 6th grade level or higher and to complete study evaluations
3. Social drinkers consuming 1- 6 standard alcoholic drinks per week and having engaged in at least one and no more than 5 binge drinking episodes in the past year.
4. BMI 19-30

Exclusion Criteria:

1. Current DSM-V abuse or dependence criteria for alcohol, dependence criteria for other substances, other than nicotine.
2. Positive test results at any appointments after the initial intake appointment on urine drug screens conducted for opiates, cocaine, marijuana, benzodiazepines and/or barbiturates.
3. Regular use of psychoactive drugs including anxiolytics and antidepressants.
4. Psychotic or otherwise severely psychiatrically disabled.
5. Medical conditions that would contraindicate the consumption of alcohol.
6. History of neurological trauma or disease, delirium, or hallucinations, or any significant systemic illness or unstable medical condition.
7. Women who are pregnant, nursing, or refuse to use a reliable method of birth control. Urine pregnancy tests will be completed at intake and prior to administration of alcohol.
8. Subjects who report disliking spirits will be excluded because hard liquor will be provided during the alcohol administration.
9. Subjects who have taken any investigational drug and/or participated in another study which involves additive blood sampling and/or interventional measures that would be considered excessive in combination with the current protocol within 4 weeks immediately preceding admission to the treatment period.
10. Subjects who report any daily drug use during the 30 days prior to randomization for the following: anxiolytics, beta blockers, central nervous system stimulants, hypnotics, non-therapeutic doses of neuroleptics and antidepressants, drugs with psychotropic activity or drugs which cause excessive sedation.
11. Subjects who have donated blood within the past six weeks.
12. Current use (within 30 days of screening) of specific psychoactive medications (e.g., typical neuroleptics, narcotic analgesics, antiparkinsonian medications, systemic corticosteroids, or medications with significant central anticholinergic activity, etc.). Current use of warfarin.
13. Current use of the following medications (CYP3A4 substrates whose metabolism may be slowed by AZD0530): carbamazepine, colchicine, cyclosporine, disopyramide, fluticasone, quinidine, vinblastine, vincristine, nifedipine. Patients taking sildenafil, tadalafil, and vardenafil will be advised to stop taking these medications for the duration of the trial. Patients cannot take the following drugs which inhibit the CYP3A4 isoenzyme: cimetidine, cyclosporine, danazol, fluconazole, grapefruit juice, HIV protease inhibitors, itraconazole, ketoconazole, macrolides, miconazole, nefazodone, omeprazole, ritonavir, and verapamil.
14. Neutropenia defined as absolute neutrophils count of <1,500/microliter.
15. Thrombocytopenia defined as platelet count <100x103/microliter.
16. Liver function tests (AST, ALT, total bilirubin) >1.5 times upper limit of normal (ULN); serum creatinine, >2 times ULN, total bilirubin>1.5 times ULN; Serum creatinine >2.0 times ULN.
17. History of interstitial lung disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 125 mg Saracatinib; 125 mg Saracatinib once daily for 8-11 days	Drug: Saracatinib; Subjects will receive 125 mg Saracatinib for 8-11 days followed by an alcohol interaction lab session; Other Names: AZD0530

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety/Tolerability of Study Medication.	Number of subjects - taking 125 mg of AZD0530 (saracatinib) over 8 days - in an alcohol drinking paradigm raising blood alcohol to 80 mg/dl who had any concerning changes in physiological or behavioral outcome measures.	8 days

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2015
• Primary Completion (Actual): March 15, 2016
• Study Completion (Actual): March 23, 2016

Study Registration Dates

• First Submitted: November 9, 2015
• First Submitted That Met QC Criteria: April 4, 2016
• First Posted (Estimate): April 8, 2016

Study Record Updates

• Last Update Posted (Actual): January 14, 2020
• Last Update Submitted That Met QC Criteria: January 10, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Drinking Behavior; Alcohol Drinking; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Saracatinib
• Other Study ID Numbers: 0602001068-2; P50AA012870 (U.S. NIH Grant/Contract)